Preparation of silica-bonded N-propyltriethylenetetramine as a recyclable solid base catalyst for the synthesis of 4,4′-(arylmethylene)bis(1H- pyrazol-5-ols)

Article abstract of DOI:10.1007/s00706-012-0910-6

Silica-bonded N-propyltriethylenetetramine was prepared via the reaction between 3-silicapropyl chloride and triethylenetetramine. This heterogeneous solid base was used as a catalyst for the synthesis of 4,4′- (arylmethylene)bis(1H-pyrazol-5-ols) by a on

Full text of DOI:10.1007/s00706-012-0910-6

Monatsh Chem (2013) 144:987–992
DOI 10.1007/s00706-012-0910-6
ORIGINAL PAPER
Preparation of silica-bonded N-propyltriethylenetetramine
as a recyclable solid base catalyst for the synthesis
of 4,40-(arylmethylene)bis(1H-pyrazol-5-ols)
•
Khodabakhsh Niknam Maryam Sadeghi Habibabad
•
•
Abdollah Deris Nasrin Aeinjamshid
Received: 5 October 2011 / Accepted: 25 December 2012 / Published online: 28 February 2013
Ó Springer-Verlag Wien 2013
Abstract Silica-bonded N-propyltriethylenetetramine was
prepared via the reaction between 3-silicapropyl chloride
and triethylenetetramine. This heterogeneous solid base was
used as a catalyst for the synthesis of 4,40-(arylmethylene)
bis(1H-pyrazol-5-ols) by a one-pot condensation of aromatic
aldehydes with 3-methyl-1-phenyl-5-pyrazolone in 72–93 %
yields. The catalyst could be recycled several times without
any additional treatment.
product yield. It also avoids the complex neutralization and
separation steps needed to recover the homogeneous base
catalysts from the reaction mixture. The recovered solid
catalysts can be readily regenerated for further use.
Pyrazoles are an important class of bioactive drug target
in the pharmaceutical industry, as they are the core structure
of numerous biologically active compounds [15, 16]. For
example, they exhibit antianxiety, antipyretic, analgesic,
and anti-inflammatory properties. 2,4-Dihydro-3H-pyrazol-
3-one derivatives including 4,40-(arylmethylene)bis(3-
methyl-1-phenyl-1H-pyrazol-5-ols) have a broad spectrum
of biological activity, being used as anti-inflammatory [17],
antipyretic [18], gastric secretion stimulatory [19], antide-
pressant [20], antibacterial [21], and antifilarial agents [22].
Moreover, the corresponding 4,40-(arylmethylene)bis(1H-
pyrazol-5-ols) are applied as fungicides [23], pesticides [24],
insecticides [25], dyestuffs [26], and as chelating and
extracting reagents for different metal ions [27].
In spite of the extensive application of 4,40-(arylmeth-
ylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols) [16], few
methods have been reported for the preparation of these
interesting compounds. These methods include application
of piperidine in ethanolic solution [28], tandem Knoeve-
nagel–Michael reaction in benzene solutions [29–31],
application of sodium dodecyl sulfate in aqueous media
[32], and electrocatalytic synthesis [33]. Nevertheless, most
of these methods suffer from limitations such as moderate
yields, long reaction times, harsh reaction conditions,
application of hazardous solvents, and/or tedious workup
procedures. Therefore, finding an efficient and a practicable
protocol for the preparation of 4,40-(arylmethylene)
bis(3-methyl-1-phenyl-1H-pyrazol-5-ols) is of obvious
importance.
Keywords Heterogeneous catalyst ꢀ Solid base ꢀ
Silica-bonded N-propyltriethylenetetramine ꢀ Catalyst ꢀ
Aldehydes ꢀ Heterocycles
Introduction
Based-catalyzed condensation and addition reactions are
important in the industrial production of drugs, fragrances,
and chemical intermediates [1–6]. In addition, solid base
catalysts are used not only for condensation reactions but
also in particular for asymmetric organic syntheses [7, 8],
other organic syntheses [9–12], and characterization of
active centers [13]. The potential use of microporous and
mesoporous base catalysts in fine chemical production is
enormous [14]. These heterogeneous catalysts are known
to suppress side reactions, which include self-condensation
and oligomerization, resulting in better selectivity and
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-012-0910-6) contains supplementary
material, which is available to authorized users.
K. Niknam (&) ꢀ M. S. Habibabad ꢀ A. Deris ꢀ N. Aeinjamshid
Department of Chemistry, Faculty of Sciences, Persian Gulf
University, 75169 Bushehr, Iran
Recently, ceric ammonium nitrate (CAN) [34], ionic
liquid under ultrasonic irradiation [35], silica-bonded
e-mail: khniknam@gmail.com
123

988
K. Niknam et al.
Scheme 1
O
OH
OH
Cl
Toluene, reflux, 18 h
(MeO)3Si
O Si
Cl
SiO2
SiO2
O
OH
H2N
N
N
NH2
1)
O
O Si
H
H
N
N
NH2
N
SiO2
H
H
H
2) wash with MeOH
O
SBNPTT
Fig. 1 TGA of SBNPTT
Fig. 2 FT-IR of SBNPTT
S-sulfonic acid [36], silica sulfuric acid [37], and sulfuric
acid [[3-(3-silicapropyl)sulfanyl]propyl]ester [38] were
reported for the synthesis of 4,40-(arylmethylene)bis-
(3-methyl-1-phenyl-1H-pyrazol-5-ols). Continuing our
studies on the application of heterogeneous catalysts in
chemical transformations [36–43], we herein describe the
preparation of silica-bonded N-propyltriethylenetetramine
(SBNPTT) as illustrated in Scheme 1 and its use as a cat-
alyst for the synthesis of 4,40-(arylmethylene)bis(3-methyl-
1-phenyl-1H-pyrazol-5-ols).
Figure 2 shows Fourier transform infrared (FT-IR)
spectra for SBNPTT. The major peaks for silica (SiO2) are
broad anti-symmetric Si–O–Si stretching from 1,240 to
1,000 cm-1 and symmetric Si–O–Si stretching near
800–785 cm-1. The band assigned to silanol groups is
located at 3,757 cm-1; its intensity is small, indicating that
most of the silanols had reacted. For the amine functional
group, the FT-IR absorption range of the H–N–H asym-
metric and symmetric stretching modes lie at 3,500 to
3,300 cm-1, overlapped with broad OH stretching bands.
Results and discussion
The N–H bending mode lies around 1,643 cm-1
.
The confirmation of the presence of a mesoporous
structure was performed by SEM and N2 adsorption–
desorption measurements. The microscopic features of the
catalyst were observed with SEM (Fig. 3). In this figure we
can see the morphology of the silica substrate.
The thermogravimetric analysis (TGA) curves of SBNPTT
show the mass loss of organic materials as they decompose
upon heating (Fig. 1). The initial weight loss from
SBNPTT up to 100 °C is due to removal of physically
adsorbed solvent and surface hydroxyl groups. The weight
loss of about 11.43 % between 250 and 340 °C and 8.93 %
between 370 and 450 °C is contributed to the thermal
decomposition of organic groups. The covalent chemical
bonds between the linker and surface imparted high ther-
mal stability to the catalyst.
Additionally, the N2 adsorption–desorption isotherm
showed a characteristic type IV isotherm, indicating the
presence of mesopores. The average pore diameter was
determined to be 8 nm by the Barret–Joyner–Halenda
(BJH) method based on the isotherm. These observations
revealed that the mesoporous structure was successfully
123

Preparation of silica-bonded
989
Table 1 Condensation reaction of 4-chlorobenzaldehyde with
5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one in the presence of
different amounts of catalysts
Entry Catalyst
Catalyst loading Time/min Yield/%a
1
2
3
4
5
6
7
8
9
No catalyst
–
24 h
20
15
13
20
20
20
30
30
\10
83
SBNPTT
SBNPTT
SBNPTT
Et3N
0.02 g
0.03 g
93
0.07 g
93
55b
0.25 mmol
0.25 mmol
0.25 mmol
Morpholine
Piperazine
70
72
Triethylenetetramine 0.25 mmol
NaOAc 0.25 mmol
58
55
Reaction conditions: 4-chlorobenzaldehyde (1 mmol), 5-methyl-2-
phenyl-2,4-dihydro-3H-pyrazol-3-one (2 mmol), 10 cm3 EtOH,
reflux
a
Isolated yield
b
Also, a by-product was observed
conditions) for the condensation reaction of various aryl
aldehydes with 3-methyl-1-phenyl-5-pyrazolone into the
corresponding 4,40-(arylmethylene)bis(3-methyl-1-phenyl-
1H-pyrazol-5-ols) (Scheme 2).
As shown in Table 2, both aromatic and heteroaromatic
aldehydes reacted with 3-methyl-1-phenyl-5-pyrazolone
to afford 4,40-(arylmethylene)bis(3-methyl-1-phenyl-1H-
pyrazol-5-ols) in excellent yields. On the other hand,
benzaldehydes with electron-donating or electron-with-
drawing groups, i.e., methyl-, methylthio-, and 3,4,5-
trimethoxybenzaldehyde (Table 2, entries 2–4) or 4-nitro-,
3-nitro-, and 4-cyanobenzaldehyde (Table 2, entries
10–12), were condensed into the corresponding 4,40-
(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols)
3b–3d and 3j–3l in high yields. 3-Pyridinecarbaldehyde,
2-thiophenecarbaldehyde, and furfural (Table 2, entries
14–16) were converted into the corresponding products 3n,
3o, and 3p in 83, 72, and 76 % yield, respectively.
2-Naphthalinecarbaldehyde was converted into correspond-
ing product 3m in 85 % yield (Table 2, entry 13). It should
be mentioned that in the case of lower isolated yields, the
conversion was not 100 % and small amounts of starting
materials remained. There were not any by-products.
The practical synthetic efficiency of this reaction was
highlighted by the reaction of terephthalaldehyde and
isophthalaldehyde with 3-methyl-1-phenyl-5-pyrazolone to
give structurally complex pyrazol-5-ol derivatives 4a, 4b
(Scheme 3).
Fig. 3 SEM of SBNPTT: scale bar a 100 lm, b 1 lm
formed. The Brunauer–Emmett–Teller (BET) surface area
using nitrogen adsorption isotherms at the temperature of
liquid nitrogen gave the results of as,BET = 83.75 m2 g-1
and a total pore volume of 19.23 cm3 g-1 (see Supple-
mentary Material).
To study the effect of catalyst loading on the conden-
sation reaction of aromatic aldehydes with 3-methyl-1-
phenyl-5-pyrazolone the reaction of 4-chlorobenzaldehyde
and 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one was
chosen as a model reaction (Table 1). The results show
clearly that SBNPTT is an effective catalyst for this con-
densation and in the absence of SBNPTT the condensation
reaction gave very low yield after 24 h. The optimal
amount of SBNPTT was 0.03 g (2.77 mol %) per 1 mmol
of aldehyde in refluxing ethanol. In addition, the result of
this condensation in the presence of commercial amines
such as triethylamine, morpholine, piperazine, and trieth-
ylenetetramine and sodium acetate is shown in Table 1.
Therefore, we employed the optimized conditions
(0.03 g mmol-1 of SBNPTT in ethanol under reflux
The possibility of recycling the catalyst SBNPTT
was examined using the reaction of 4-chlorobenzaldehyde
and 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one under
the optimized conditions. Upon completion, the reaction
mixture was washed with warm ethanol (3 9 30 cm3). The
123

990
K. Niknam et al.
recovered catalyst was washed with diethyl ether, dried,
and reused for subsequent runs. The recycled catalyst was
reused six times without any additional treatment. No
appreciable loss in the catalytic activity of SBNPTT was
observed (Fig. 4).
In conclusion, we have prepared some 4,40-(arylmethyl-
ene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols) by a tandem
condensation reaction of aromatic aldehydes with two
equivalents of 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-
3-one in the presence of SBNPTT as a solid base catalyst in
refluxing ethanol.
characterized by comparison of their IR, 1H NMR, and 13
C
NMR spectroscopic data and their melting points with
reported values [29–38].
Preparation of silica-bonded N-propyltriethylenetetramine
(SBNPTT)
Chloropropyl silica was prepared by a known procedure as
previously reported [46]. To a mixture of 25 g chloropropyl
silica in 250 cm3 anhydrous xylene, 25 cm3 of triethylene-
tetramine was added and the mixture was refluxed with
stirring for 24 h. The reaction was then stopped and the
modified silica was cooled to room temperature, transferred
to a vacuum glass filter, and washed with xylene and a large
excess of ethanol in turn. The resulting SBNPTT was dried
under vacuum overnight at 80 °C and 26.4 g was obtained.
The pH of 0.1 g of this solid base at 25 °C was determined
by a pH-ISE conductivity titration controller (Denver
Instrument Model 270) to be 9.7.
Experimental
Chemicals were purchased from Fluka, Merck, and
Aldrich. All the products are known compounds and were
Scheme 2
O
O Si
N
H
N
N
NH2
Me
SiO2
Ar
H
H
Me
Me
O
2
Ar-CHO +
N
N
N
N
O
N
EtOH, reflux
N
Ph
OH HO
Ph
Ph
1
2
3a-3p
Table 2 Preparation of 4,40-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol) derivatives catalyzed by SBNPTT in ethanol under re-
fluxing conditions
Entry
Ar (1)
Product
Time/min
Yield/%a
M.p./°C
Lit. m.p./°C
1
C6H5-
3a
3b
3c
3d
3e
3f
30
35
90
89
91
90
86
88
93
90
87
89
90
88
85
83
72
76
82
84
170–172
202–204
201–203
195–197
227–229
198–200
215–217
227–229
181–183
225–227
151–153
210–212
206–208
238–240
181–183
189–191
191–192
214–216
171–172 [32]
203 [29]
2
4-Me-C6H4-
4-MeS-C6H4-
3,4,5-(MeO)3-C6H2-
2-HO-C6H4-
2-Br-C6H4-
3
35
201–203 [36]
195–197 [38]
230–231 [33]
198–200 [38]
210 [29]
4
45
5
35
6
20
7
4-Cl-C6H4-
3g
3h
3i
15
8
2,4-(Cl)2-C6H3-
4-F-C6H4-
20
228–230 [32]
182 [29]
9
35
10
11
12
13
14
15
16
17
18
4-O2N-C6H4-
3-O2N-C6H4-
4-(CN)-C6H4-
2-Naphthalenyl-
3-Pyridyl-
3j
60
224–226 [32]
149–150 [32]
210–212 [36]
206–208 [37]
238–240 [37]
181–183 [36]
189–190 [44]
190–194 [45]
218–220 [45]
3k
3l
70
35
3m
3n
3o
3p
4a
4b
100
120
120
120
120
120
2-Thienyl-
2-Furanyl-
3-OHC-C6H4-
4-OHC-C6H4-
Reaction conditions: aromatic aldehyde (1 mmol), 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one (2 mmol), 0.03 g catalyst SBNPTT,
10 cm3 EtOH, reflux
a
Isolated yield
123

Preparation of silica-bonded
991
Scheme 3
Ph
N
OH
HO
N
Ph
N
N
Me
Me
SBNPTT
CHO
+
Me
Me
OHC
4
N
EtOH, reflux
O
Me
N
Ph
N
N
N
2
N
OH HO
Ph
Ph
4a, 4b
¨
3. Dorwald FZ (ed) (2002) Organic synthesis on solid phase. Wiley,
Weinheim
4. Toy PH, Lam Y (eds) (2012) Solid-phase organic synthesis:
concepts, strategies, and applications. Wiley, Weinheim
5. Sheldon RA, van Bekkum H (eds) (2001) Fine chemicals through
heterogeneous catalysis: Solid base catalysts, chap 7. Wiley-
VCH, Weinheim, pp 309–350
6. Sheldon RA, Arends I, van Rantwijk F (eds) (2006) Green
chemistry and catalysis. Wiley, Weinheim
´
7. Bartok M (2010) Chem Rev 110:1663
8. Ding K, Uozumi Y (eds) (2008) Handbook of asymmetric het-
erogeneous catalysis. Wiley-VCH, Weinheim
9. Yokoi T, Kubota Y, Tatsumi T (2012) Appl Catal A Gen
421:14
10. Tang Y, Chen G, Lu Y (2012) Res Chem Intermed 38:937
Fig. 4 Recyclability of SBNPTT as catalyst in the condensation
reaction of 4-chlorobenzaldehyde (1 mmol) and 5-methyl-2-phenyl-
2,4-dihydro-3H-pyrazol-3-one (2 mmol) in the presence of 0.03 g of
SBNPTT in refluxing ethanol. Reaction time 15 min
´
¨ ¨
11. Szollosi G, Bartok M (1999) J Mol Struct 482:13
´
¨ ¨
12. Szollosi G, Bartok M (1999) Catal Lett 59:179
13. Tsuchiya S, Morishige H, Imamura H (1991) J Catal 129:303
14. Weitkamp J, Hunger M, Rymsa U (2001) Micropor Mesopor
Mater 48:255
General procedure for the synthesis of 4,40-
(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols
15. McDonald E, Jones K, Brough PA, Drysdale MJ, Workman P
(2006) Curr Top Med Chem 6:1193
16. Elderfield RC (ed) (1957) Heterocyclic compounds, vol 5. Wiley,
New York
Aromatic aldehyde (1 mmol) was added to a flask con-
taining a mixture of 5-methyl-2-phenyl-2,4-dihydro-3H-
pyrazol-3-one (2 mmol) and 0.03 g SBNPTT (2.77 mol %)
in 10 cm3 warm ethanol and heated under reflux for an
appropriate time. After completion of the reaction, as
indicated by TLC, the reaction mixture was washed with
warm ethanol (3 9 30 cm3). After cooling the crude
products were precipitated and purified by recrystallization
from ethanol (95 %). The recovered catalyst was washed
with diethyl ether, dried, and reused for subsequent runs.
17. Elguero J (1996) In: Katritzky AR, Rees CW, Scriven EFV (eds)
Comprehensive heterocyclic chemistry, vol 5. Pergamon, Oxford
18. Elguero J, Goya P, Jagerovic N, Silva AMS (2002) Targets
Heterocycl Syst 6:52
19. Sugiura S, Ohno S, Ohtani O, Izumi K, Kitamikado T, Asai T,
Kato K (1977) J Med Chem 20:80
20. Behr LC, Fusco R, Jarboe CH (1967) In: Weissberger A (ed) The
chemistry of heterocyclic compounds: pyrazoles, pyrazolines,
pyrazolidines, indazoles and condensed rings. Interscience, New
York
21. Rosiere CE, Grossman MI (1951) Science 113:651
22. Bailey DM, Hansen PE, Hlavac AG, Baizman ER, Pearl J,
Defelice AF, Feigenson ME (1985) J Med Chem 28:256
23. Mahajan RN, Havaldar FH, Fernandes PS (1991) J Indian Chem
Soc 68:245
Acknowledgments We are thankful to the Persian Gulf University
Research Council for the partial support of this work. Also, we are
thankful to the School of Chemistry, Manchester University for
running NMR, BET, CHN, TGA, and SEM.
24. Chauhan PMS, Singh S, Chatterjee RK (1993) Indian J Chem
Sect B 32:858
25. Singh D, Singh D (1991) J Indian Chem Soc 68:165
26. Uzoukwu AB (1993) Polyhedron 12:2719
27. Garnovskii AD, Uraev AI, Minkin VI (2004) Arkivoc iii:29
28. Singh D, Singh D (1984) J Chem Eng Data 29:355
29. Li XL, Wang YM, Tian B, Matsuura T, Meng JB (1998) J Het-
erocycl Chem 35:129
References
1. Kelly GJ, King F, Kett M (2002) Gr Chem 4:392
¨
30. Pavlov PT, Goleneva AF, Lesnov AE, Prokhorova TS (1998)
Pharm Chem J (Engl Trans) 32:370
2. Ertl G, Knozinger H, Weitkamp J (eds) (1997) Handbook of
heterogeneous catalysis. VCH, Weinheim
123

992
K. Niknam et al.
31. Sivaprasad G, Perumal PT, Prabavathy VR, Mathivanan N (2006)
Bioorg Med Chem Lett 16:6302
39. Niknam K, Zolfigol MA, Khorramabadi-Zad A, Zare R, Shayegh
M (2006) Catal Commun 7:494
32. Wang W, Wang SX, Qin XY, Li JT (2005) Synth Commun
35:1263
33. Elinson MN, Dorofeev AS, Nasybullin RF, Nikishin GI (2008)
Synthesis 1933
34. Sujatha K, Shanthi G, Selvam NP, Manoharan S, Perumal PT,
Rajendran M (2009) Bioorg Med Chem Lett 19:4501
35. Zang H, Su Q, Mo Y, Cheng B (2011) Ultrason Sonochem 18:68
36. Niknam K, Saberi D, Sadegheyan M, Deris A (2010) Tetrahedron
Lett 51:962
37. Niknam K, Mirzaee S (2011) Synth Commun 41:2403
38. Tayebi S, Baghernejad M, Saberi D, Niknam K (2011) Chin J
Catal 32:1477
40. Niknam K, Karami B, Zolfigol MA (2007) Catal Commun 8:1427
41. Niknam K, Saberi D, Nouri Sefat M (2009) Tetrahedron Lett
50:4058
42. Niknam K, Saberi D (2009) Appl Catal A Gen 366:220
43. Niknam K, Saberi D (2009) Tetrahedron Lett 50:5210
44. Niknam K, Deris A, Naeimi F, Majleci F (2011) Tetrahedron Lett
52:4642
45. Reiner K, Richter R, Hauptmann S, Becher J, Hennig L (1995)
Tetrahedron 51:13291
46. Baghernejad M, Niknam K (2012) Int J Chem 4:52
123